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Mechanisms underlying the effect of infection and inflammation on ovarian health. / Jennifer Claire Price

Swansea University Author: Jennifer Claire Price

Abstract

Bacterial contamination of the female genital tract after parturition is common and subsequent infections are associated with infertility. Infections of the uterus or mammary gland in cattle perturb ovarian function, with decreased dominant follicle growth rate and delayed ovulation. Granulosa cells...

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Published: 2013
Institution: Swansea University
Degree level: Doctoral
Degree name: Ph.D
URI: https://cronfa.swan.ac.uk/Record/cronfa42833
first_indexed 2018-08-02T18:55:39Z
last_indexed 2019-10-21T16:48:32Z
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recordtype RisThesis
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spelling 2018-08-29T15:09:26.9308809 v2 42833 2018-08-02 Mechanisms underlying the effect of infection and inflammation on ovarian health. 765156d6c54d490cf70168ded55e29f5 NULL Jennifer Claire Price Jennifer Claire Price true true 2018-08-02 Bacterial contamination of the female genital tract after parturition is common and subsequent infections are associated with infertility. Infections of the uterus or mammary gland in cattle perturb ovarian function, with decreased dominant follicle growth rate and delayed ovulation. Granulosa cells that line ovarian follicles express the molecular machinery necessary to respond to common bacterial pathogen-associated molecular patterns (PAMPs), suggesting that granulosa cells may play a role in ovarian innate immunity.In the present thesis, the effect of bacterial PAMPs on ovarian follicle cells was examined during follicular growth, from emergence through dominance, and the early stages of embryogenesis. Granulosa cells from emerged or dominant bovine follicles increased production of inflammatory mediators, such as IL-6 and IL-8, through Toll-like receptor (TLR)-dependent pathways in response to the PAMPs lipopolysaccharide and the synthetic triacylated lipopeptide Pam3CSK4. The requirement for TLR2 and TLR4 was confirmed by using siRNA, showing activation of MAPK intracellular pathways and inhibiting key signals (p38, MEK or NFkB) in TLR pathways. The endocrine function of granulosa cells was perturbed by PAMPs, with decreased oestradiol and progesterone output. In addition, the endocrine environment affected granulosa cellular responses, with high EGF increasing the cellular response to PAMPs. Bacterial PAMPs also perturbed the oocyte, with increased cumulus expansion and parthenote cleavage rate, as well as changes in key genes involved in oocyte maturation. Finally, a human granulosa cell line was used to examine if PAMPs perturb human as well as bovine ovarian health. Indeed, human cells also expressed TLRs and mounted a cellular response to PAMPs at the mRNA level.This thesis provides a molecular mechanism for the perturbation of ovarian function by an infection at a site distal to the ovary. E-Thesis Granulosa cells, bacteria, infertility, infection 31 12 2013 2013-12-31 COLLEGE NANME Swansea University Medical School COLLEGE CODE Swansea University Doctoral Ph.D 2018-08-29T15:09:26.9308809 2018-08-02T16:24:30.5857971 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Jennifer Claire Price NULL 1 0042833-02082018162525.pdf 10821223.pdf 2018-08-02T16:25:25.4670000 Output 19921317 application/pdf E-Thesis true 2018-08-02T16:25:25.4670000 false
title Mechanisms underlying the effect of infection and inflammation on ovarian health.
spellingShingle Mechanisms underlying the effect of infection and inflammation on ovarian health.
Jennifer Claire Price
title_short Mechanisms underlying the effect of infection and inflammation on ovarian health.
title_full Mechanisms underlying the effect of infection and inflammation on ovarian health.
title_fullStr Mechanisms underlying the effect of infection and inflammation on ovarian health.
title_full_unstemmed Mechanisms underlying the effect of infection and inflammation on ovarian health.
title_sort Mechanisms underlying the effect of infection and inflammation on ovarian health.
author_id_str_mv 765156d6c54d490cf70168ded55e29f5
author_id_fullname_str_mv 765156d6c54d490cf70168ded55e29f5_***_Jennifer Claire Price
author Jennifer Claire Price
author2 Jennifer Claire Price
format E-Thesis
publishDate 2013
institution Swansea University
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
document_store_str 1
active_str 0
description Bacterial contamination of the female genital tract after parturition is common and subsequent infections are associated with infertility. Infections of the uterus or mammary gland in cattle perturb ovarian function, with decreased dominant follicle growth rate and delayed ovulation. Granulosa cells that line ovarian follicles express the molecular machinery necessary to respond to common bacterial pathogen-associated molecular patterns (PAMPs), suggesting that granulosa cells may play a role in ovarian innate immunity.In the present thesis, the effect of bacterial PAMPs on ovarian follicle cells was examined during follicular growth, from emergence through dominance, and the early stages of embryogenesis. Granulosa cells from emerged or dominant bovine follicles increased production of inflammatory mediators, such as IL-6 and IL-8, through Toll-like receptor (TLR)-dependent pathways in response to the PAMPs lipopolysaccharide and the synthetic triacylated lipopeptide Pam3CSK4. The requirement for TLR2 and TLR4 was confirmed by using siRNA, showing activation of MAPK intracellular pathways and inhibiting key signals (p38, MEK or NFkB) in TLR pathways. The endocrine function of granulosa cells was perturbed by PAMPs, with decreased oestradiol and progesterone output. In addition, the endocrine environment affected granulosa cellular responses, with high EGF increasing the cellular response to PAMPs. Bacterial PAMPs also perturbed the oocyte, with increased cumulus expansion and parthenote cleavage rate, as well as changes in key genes involved in oocyte maturation. Finally, a human granulosa cell line was used to examine if PAMPs perturb human as well as bovine ovarian health. Indeed, human cells also expressed TLRs and mounted a cellular response to PAMPs at the mRNA level.This thesis provides a molecular mechanism for the perturbation of ovarian function by an infection at a site distal to the ovary.
published_date 2013-12-31T04:25:36Z
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